The role of protein phosphorylation in the action of vasopressin is being investigated using as a model a strain of mice with hereditary vasopressin-resistant diabetes insipidus. This strain of mice appears to have a specific defect in the response to vasopressin which occurs at a step beyond the generation of the second messenger, cyclic AMP. When the proteins in homogenates of renal medulla are labelled with 32P in the presence of cyclic AMP those obtained from kidneys of mice with diabetes insipidus appear to lack two phosphoproteins, both of which are present in similarly treated homogenates from normal mice. Our present purpose is to explore the possiblity that absence of these phosphoproteins is related to vasopressin resistance.